Journal of Virology, August 2003, p. 9069-9073, Vol. 77, No. 16
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.16.9069-9073.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Role of the Human Immunodeficiency Virus Type 1 Envelope Gene in Viral Fitness
Hector R. Rangel,1 Jan Weber,1 Bikram Chakraborty,1 Arantxa Gutierrez,2 Michael L. Marotta,1 Muneer Mirza,1 Patti Kiser,1 Miguel A. Martinez,2 Jose A. Este,2 and Miguel E. Quiñones-Mateu1,3*
Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation,1
Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio,3
Laboratori de Retrovirologia, Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain2
Received 21 April 2003/
Accepted 30 May 2003
A human host offers a variety of microenvironments to the infecting human immunodeficiency virus type 1 (HIV-1), resulting in various selective pressures, most of them directed against the envelope (env) gene. Therefore, it seems evident that the replicative capacity of the virus is largely related to viral entry. In this study we have used growth competition experiments and TaqMan real-time PCR detection to measure the fitness of subtype B HIV-1 primary isolates and autologous env-recombinant viruses in order to analyze the contribution of wild-type env sequences to overall HIV-1 fitness. A significant correlation was observed between fitness values obtained for wild-type HIV-1 isolates and those for the corresponding env-recombinant viruses (r = 0.93; P = 0.002). Our results suggest that the env gene, which is linked to a myriad of viral characteristics (e.g., entry into the host cell, transmission, coreceptor usage, and tropism), plays a major role in fitness of wild-type HIV-1. In addition, this new recombinant assay may be useful for measuring the contribution of HIV-1 env to fitness in viruses resistant to novel antiretroviral entry inhibitors.
* Corresponding author. Mailing address: Cleveland Clinic Foundation, Lerner Research Institute, Department of Virology/NN10, 9500 Euclid Ave., Cleveland, OH 44195. Phone: (216) 444-2515. Fax: (216) 444-2998. E-mail: quinonm{at}ccf.org.
Journal of Virology, August 2003, p. 9069-9073, Vol. 77, No. 16
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.16.9069-9073.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.